PT  - JOURNAL ARTICLE
AU  - Natalie Terzikhan
AU  - Hanfei Xu
AU  - Ahmed Edris
AU  - Ken R. Bracke
AU  - Fien M. Verhamme
AU  - Bruno H.C. Stricker
AU  - Josée Dupuis
AU  - Lies Lahousse
AU  - George T. O'Connor
AU  - Guy G. Brusselle
TI  - Epigenome-wide association study on diffusing capacity of the lung
AID  - 10.1183/23120541.00567-2020
DP  - 2021 Jan 01
TA  - ERJ Open Research
PG  - 00567-2020
VI  - 7
IP  - 1
4099  - http://openres.ersjournals.com/content/7/1/00567-2020.short
4100  - http://openres.ersjournals.com/content/7/1/00567-2020.full
SO  - erjor2021 Jan 01; 7
AB  - Background Epigenetics may play an important role in the pathogenesis of lung diseases. However, little is known about the epigenetic factors that influence impaired gas exchange at the lung.Aim To identify the epigenetic signatures of the diffusing capacity of the lung measured by carbon monoxide uptake (the diffusing capacity of the lung for carbon monoxide (DLCO)).Methods An epigenome-wide association study (EWAS) was performed on diffusing capacity, measured by carbon monoxide uptake (DLCO) and per alveolar volume (VA) (as DLCO/VA), using the single-breath technique in 2674 individuals from two population-based cohort studies. These were the Rotterdam Study (RS, the “discovery panel”) and the Framingham Heart Study (FHS, the “replication panel”). We assessed the clinical relevance of our findings by investigating the identified sites in whole blood and by lung tissue specific gene expression.Results We identified and replicated two CpG sites (cg05575921 and cg05951221) that were significantly associated with DLCO/VA and one (cg05575921) suggestively associated with DLCO. Furthermore, we found a positive association between aryl hydrocarbon receptor repressor (AHRR) gene (cg05575921) hypomethylation and gene expression of exocyst complex component 3 (EXOC3) in whole blood. We confirmed that the expression of EXOC3 in lung tissue is positively associated with DLCO/VA and DLCO.Conclusions We report on epigenome-wide associations with diffusing capacity in the general population. Our results suggest EXOC3 to be an excellent candidate, through which smoking-induced hypomethylation of AHRR might affect pulmonary gas exchange.Epigenetic changes, including smoking-induced hypomethylation, may affect pulmonary gas exchange https://bit.ly/3k4ZdvH